8dwt

From Proteopedia

(Difference between revisions)

Current revision

SPOP W22R Form 2

Structural highlights

8dwt is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 6.2Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SPOP_HUMAN Inhibits IPF1/PDX1 transactivation of established target promoters, such as insulin, may be by recruiting a repressor complex (By similarity). In complex with CUL3, involved in ubiquitination of BMI1, H2AFY and DAXX, and probably also in ubiquitination and proteasomal degradation of Gli2 or Gli3.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The speckle-type POZ protein (SPOP) functions in the Cullin3-RING ubiquitin ligase (CRL3) as a receptor for the recognition of substrates involved in cell growth, survival, and signaling. SPOP mutations have been attributed to the development of many types of cancers, including prostate and endometrial cancers. Prostate cancer mutations localize in the substrate-binding site of the substrate recognition (MATH) domain and reduce or prevent binding. However, most endometrial cancer mutations are dispersed in seemingly inconspicuous solvent-exposed regions of SPOP, offering no clear basis for their cancer-causing and peculiar gain-of-function properties. Herein, we present the first structure of SPOP in its oligomeric form, uncovering several new interfaces important for SPOP self-assembly and normal function. Given that many previously unaccounted-for cancer mutations are localized in these newly identified interfaces, we uncover molecular mechanisms underlying dysregulation of SPOP function, with effects ranging from gross structural changes to enhanced self-association, and heightened stability and activity.

Higher-order SPOP assembly reveals a basis for cancer mutant dysregulation.,Cuneo MJ, O'Flynn BG, Lo YH, Sabri N, Mittag T Mol Cell. 2023 Mar 2;83(5):731-745.e4. doi: 10.1016/j.molcel.2022.12.033. Epub , 2023 Jan 23. PMID:36693379^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Furukawa M, He YJ, Borchers C, Xiong Y. Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases. Nat Cell Biol. 2003 Nov;5(11):1001-7. Epub 2003 Oct 5. PMID:14528312 doi:10.1038/ncb1056
↑ Hernandez-Munoz I, Lund AH, van der Stoop P, Boutsma E, Muijrers I, Verhoeven E, Nusinow DA, Panning B, Marahrens Y, van Lohuizen M. Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7635-40. Epub 2005 May 16. PMID:15897469 doi:0408918102
↑ Kwon JE, La M, Oh KH, Oh YM, Kim GR, Seol JH, Baek SH, Chiba T, Tanaka K, Bang OS, Joe CO, Chung CH. BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase. J Biol Chem. 2006 May 5;281(18):12664-72. Epub 2006 Mar 8. PMID:16524876 doi:10.1074/jbc.M600204200
↑ Cuneo MJ, O'Flynn BG, Lo YH, Sabri N, Mittag T. Higher-order SPOP assembly reveals a basis for cancer mutant dysregulation. Mol Cell. 2023 Mar 2;83(5):731-745.e4. PMID:36693379 doi:10.1016/j.molcel.2022.12.033

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8dwt"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8dwt is ON HOLD
+==SPOP W22R Form 2==
+<StructureSection load='8dwt' size='340' side='right'caption='[[8dwt]], [[Resolution|resolution]] 6.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8dwt]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DWT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DWT FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 6.2&#8491;</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8dwt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dwt OCA], [https://pdbe.org/8dwt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dwt RCSB], [https://www.ebi.ac.uk/pdbsum/8dwt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dwt ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/SPOP_HUMAN SPOP_HUMAN] Inhibits IPF1/PDX1 transactivation of established target promoters, such as insulin, may be by recruiting a repressor complex (By similarity). In complex with CUL3, involved in ubiquitination of BMI1, H2AFY and DAXX, and probably also in ubiquitination and proteasomal degradation of Gli2 or Gli3.<ref>PMID:14528312</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The speckle-type POZ protein (SPOP) functions in the Cullin3-RING ubiquitin ligase (CRL3) as a receptor for the recognition of substrates involved in cell growth, survival, and signaling. SPOP mutations have been attributed to the development of many types of cancers, including prostate and endometrial cancers. Prostate cancer mutations localize in the substrate-binding site of the substrate recognition (MATH) domain and reduce or prevent binding. However, most endometrial cancer mutations are dispersed in seemingly inconspicuous solvent-exposed regions of SPOP, offering no clear basis for their cancer-causing and peculiar gain-of-function properties. Herein, we present the first structure of SPOP in its oligomeric form, uncovering several new interfaces important for SPOP self-assembly and normal function. Given that many previously unaccounted-for cancer mutations are localized in these newly identified interfaces, we uncover molecular mechanisms underlying dysregulation of SPOP function, with effects ranging from gross structural changes to enhanced self-association, and heightened stability and activity.
-Authors: Cuneo, M.J., Mittag, T., O''Flynn, B., Lo, Y.H.
+Higher-order SPOP assembly reveals a basis for cancer mutant dysregulation.,Cuneo MJ, O'Flynn BG, Lo YH, Sabri N, Mittag T Mol Cell. 2023 Mar 2;83(5):731-745.e4. doi: 10.1016/j.molcel.2022.12.033. Epub , 2023 Jan 23. PMID:36693379<ref>PMID:36693379</ref>
-Description: SPOP W22R Tetrameric Form
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Mittag, T]]
+<div class="pdbe-citations 8dwt" style="background-color:#fffaf0;"></div>
-[[Category: Cuneo, M.J]]
-[[Category: Lo, Y.H]]
+==See Also==
-[[Category: O''Flynn, B]]
+*[[Speckle-type POZ protein 3D structures|Speckle-type POZ protein 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Cuneo MJ]]
+[[Category: Lo YH]]
+[[Category: Mittag T]]
+[[Category: O'Flynn B]]

8dwt

From Proteopedia

Current revision

SPOP W22R Form 2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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